Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary

Background & Aims: Maternal liver shows robust adaptations to pregnancy to accommodate the metabolic needs of the developing and growing placenta and fetus by largely unknown mechanisms. We found that Ascl1, a gene encoding a basic helix-loop-helix transcription factor essential for neuronal...

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Autores principales:	Joonyong Lee, Veronica Garcia, Shashank M. Nambiar, Huaizhou Jiang, Guoli Dai
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Hepatocyte Gestation Insulin-Like Growth Factor 2 Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/165a3a92609648a8bed004968ca771bb
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spelling	oai:doaj.org-article:165a3a92609648a8bed004968ca771bb2021-11-12T04:39:39ZActivation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary2352-345X10.1016/j.jcmgh.2021.08.009https://doaj.org/article/165a3a92609648a8bed004968ca771bb2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001764https://doaj.org/toc/2352-345XBackground & Aims: Maternal liver shows robust adaptations to pregnancy to accommodate the metabolic needs of the developing and growing placenta and fetus by largely unknown mechanisms. We found that Ascl1, a gene encoding a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice. Methods: To investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from midgestation until term. Results: As a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 showed aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and increased release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta showed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 showed robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments. Conclusions: In summary, we show that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies show that Ascl1 is a novel and critical regulator of the physiology of pregnancy.Joonyong LeeVeronica GarciaShashank M. NambiarHuaizhou JiangGuoli DaiElsevierarticleHepatocyteGestationInsulin-Like Growth Factor 2Diseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 1, Pp 35-55 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatocyte Gestation Insulin-Like Growth Factor 2 Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Hepatocyte Gestation Insulin-Like Growth Factor 2 Diseases of the digestive system. Gastroenterology RC799-869 Joonyong Lee Veronica Garcia Shashank M. Nambiar Huaizhou Jiang Guoli Dai Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
description	Background & Aims: Maternal liver shows robust adaptations to pregnancy to accommodate the metabolic needs of the developing and growing placenta and fetus by largely unknown mechanisms. We found that Ascl1, a gene encoding a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice. Methods: To investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from midgestation until term. Results: As a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 showed aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and increased release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta showed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 showed robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments. Conclusions: In summary, we show that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies show that Ascl1 is a novel and critical regulator of the physiology of pregnancy.
format	article
author	Joonyong Lee Veronica Garcia Shashank M. Nambiar Huaizhou Jiang Guoli Dai
author_facet	Joonyong Lee Veronica Garcia Shashank M. Nambiar Huaizhou Jiang Guoli Dai
author_sort	Joonyong Lee
title	Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
title_short	Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
title_full	Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
title_fullStr	Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
title_full_unstemmed	Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary
title_sort	activation of proneuronal transcription factor ascl1 in maternal liver ensures a healthy pregnancysummary
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/165a3a92609648a8bed004968ca771bb
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Activation of Proneuronal Transcription Factor Ascl1 in Maternal Liver Ensures a Healthy PregnancySummary

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